Do Orthotopic Ileal Diversions Induce Immunological Changes in Retained Urethral Tissue?

BACKGROUND: A second primary tumors of the urethra (urethral recurrence) after radical cystectomy has been reported to be more infrequent in patients with ileal orthotopic (neobladder) compared to incontinent diversions. OBJECTIVE: To investigate whether an altered immunogenic environment of urethral tissue is induced by urethro-ileal anastomosis. METHODS: Between 10/2008 and 12/2009 urethral biopsies of 19 patients (9 neobladder patients, 10 control patients without urethra-ileal anastomosis) were evaluated by conventional histopathological examination and immunohistochemistry for T- (CD3/CD5, CD4, CD8) and B-cell markers (CD20/22, CD79a, CD138). After semi-quantitative assessment, relative cell fractions (B vs. T cells) and subclasses (T4-helper vs. T8-killer cells vs. B cell clones, plasma cells) in neobladder vs. control patients were studied. Unpaired t-test was used for statistical analysis. RESULTS: Of 19 included patients, 16 were eligible for analysis (7x neobladder, 9x controls). All neobladder patients had undergone cystectomy for UBC. Comparing relative fractions of cells positive for T- and B-cell markers in NB and CO patients, no statistical differences were observed. In 4/7 neobladder patients relative fraction of CD79a positive B-cells was higher than relative fraction of CD3/CD5 positive T-cells (B/T-ratio 1.3). B cells were predominantly CD138 positive plasma cells (5/7 NB patients). Relative B-cell fraction was lower than T-cell fraction in 7/9 control patients (B/T-ratio 0.6). Neither CD 138 positive plasma cells nor CD22 positive B cell clones were predominant. T-helper and CD8 positive T-killer cells were equally distributed in both neobladder (CD4/CD8-ratio: 2.1) and control patients (CD4/CD8-ratio: 1.9). CONCLUSIONS: Comparing neobadder and control patients the distribution of B- and T-cells was statistically not different. However, a trend towards an increased presence of B-cells in urethral tissues of NB patients that could become relevant in a larger study might be suggestive for an immunological response induced by connecting urethral and ileal tissue.

The clinical epidemiology of urachal carcinoma: results of a large, population based study.

PURPOSE: Survival data on urachal carcinoma are sparse due to the low prevalence of this cancer. We report urachal carcinoma clinical outcomes and prognostic factors in a large, population based cohort of patients with long-term followup. MATERIALS AND METHODS: Data were collected from the nationwide Netherlands Cancer Registry. Urachal carcinoma cases were also cross-referenced using the PALGA (Nationwide Network and Registry of Histology and Cytopathology) database. Pathology report summaries were reviewed. A total of 152 patients diagnosed with urachal carcinoma between 1989 and 2009 were included in analysis. The Sheldon staging system was used to classify urachal carcinoma. Median followup was 9.2 years. Primary outcomes were overall and relative survival. Prognostic factors were calculated using univariate and multivariate hazard regression models. RESULTS: The incidence of urachal carcinoma was 0.2% of all bladder cancers. A total of 45 patients (30%) presented with lymph node or distant metastasis. Five-year overall and relative survival was 45% and 48%, respectively. On multivariate analysis prognostic factors for impaired survival were lymph node metastasis (HR 1.7, 95% CI 1.2-2.6), tumor growth in the abdominal wall, peritoneum and/or adjacent organs (HR 5.2, 95% CI 2.6-10.3), distant metastasis (HR 5.3, 95% CI 2.8-9.9) and macroscopic residual tumor (HR 5.2, 95% CI 1.2-21.8). CONCLUSIONS: Urachal carcinoma is rare, accounting for 0.2% of all bladder cancers. Many patients present with advanced disease. The prognosis of urachal carcinoma depends mostly on tumor stage, particularly the presence or absence of metastatic disease.

Discrepancy between clinical staging through bimanual palpation and pathological staging after cystectomy.

OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Prognostic factors for survival in patients with recurrence of muscle invasive bladder cancer after treatment with curative intent.

UNLABELLED: Prognostic factors for survival after recurrent MIBC are unknown and were evaluated using a population-based series of 1409 MIBC patients. 330 Patients who underwent RC or RT with curative intent and who suffered from recurrence were selected. Multivariable survival analyses were performed. Clinicopathological factors that predict survival after recurrence are recurrence location, treatment for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study to evaluate the prognostic factors for survival among patients with recurrent muscle-invasive bladder cancer (MIBC) after initial treatment with curative intent. PATIENTS AND METHODS: Clinical data were collected from a population-based series of 1409 patients with MIBC. We selected 330 patients who underwent radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with curative intent and who experienced recurrence. Multivariate survival analyses were performed with death from MIBC as the endpoint. Covariates were gender, time to recurrence, age at diagnosis of recurrence, recurrence multiplicity, localization, and treatment for recurrence. Analyses were performed separately for patients initially treated with RC (i-RC) or external beam radiotherapy (i-EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year survival of 17% and 6%, respectively. Localization and treatment for recurrence were significantly associated with survival. Patients with recurrence after i-EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at diagnosis of recurrence, localization, and treatment for recurrence were significantly associated with survival. CONCLUSION: This study confirms the extremely poor prognosis after recurrence of MIBC in patients initially treated with surgery or RT. Clinicopathologic factors that predict survival after disease recurrence are location of recurrence, treatment for recurrence, and age at diagnosis of recurrence. Improved diagnosis of primary MIBC to detect extravesical disease and more effective therapeutic approaches to target recurrent MIBC are needed.

Clinical epidemiology of nonurothelial bladder cancer: analysis of the Netherlands Cancer Registry.

PURPOSE: Nonurothelial malignancies represent a small fraction of bladder malignancies and are less extensively studied, resulting in sparse empirical data on these tumors. We sought insight into tumor characteristics and survival. MATERIALS AND METHODS: Data were obtained from the nationwide Netherlands Cancer Registry on patient and tumor characteristics, and followup in all patients with primary invasive (T1 or greater) bladder tumors in The Netherlands between 1995 and 2006. Data were analyzed using frequency tables. Relative survival analysis was done. RESULTS: We identified 28,807 patients with invasive bladder cancer, of whom 7.7% presented with nonurothelial carcinoma. Mean patient age range at diagnosis of adenocarcinoma and soft tissue tumors was 66.4 years, and 78.3 years at diagnosis of nonspecified tumors. Most histological subtypes were more common in males except squamous cell carcinoma and lymphoma. Muscle invasion was seen in 52.2% of urothelial carcinoma cases vs 87.5%, 71.9% and 89.0% of squamous cell carcinoma, adenocarcinoma and neuroendocrine tumor cases, respectively. For urothelial carcinoma, squamous cell carcinoma and adenocarcinoma women presented at more advanced stage. In the neuroendocrine group this stage difference was the opposite. Survival analysis showed a 5-year relative survival rate of 32.2%, 22.9%, 31.8% and 21.1% for T2 or greater urothelial carcinoma, squamous cell carcinoma, adenocarcinoma and neuroendocrine tumors, respectively. CONCLUSIONS: Patients with nonurothelial carcinoma present at more advanced stage and overall have worse survival. Relative survival of muscle invasive adenocarcinoma equals survival of muscle invasive urothelial carcinoma. For stage II and III disease these cases do even better. Muscle invasive squamous cell carcinoma and neuroendocrine tumors show worse survival regardless of stage.

Brachytherapy versus cystectomy in solitary bladder cancer: a case control, multicentre, East-Netherlands study.

PURPOSE: Comparing the outcome of surgery and brachytherapy-based radiotherapy in patients with solitary T1G3/T2 bladder tumour in, a retrospective case-control study, because efforts for a randomised clinical trial comparing these modalities have failed. MATERIALS AND METHODS: Cystectomy group. Patients were selected using the pathological registration system (PALGA). 289 cases of TURT followed by cystectomy, indicated by a muscle--invading bladder tumour were performed in three East-Netherlands medical centres between 1991 and 2001. Out of this group 179 patients with clinical T2N0M0 bladder tumour were selected. All the consecutive files were analysed by a urologist and a radiation oncologist and 65 of those patients (mean age 63.7 years) would have been eligible for brachytherapy, based on an initial analysis: cystoscopy estimated tumour size, post-TURT pathological report, completed by CT-scan and/or, MRI-scan. A final pathological report after radical cystectomy was not considered for patients' selection. Brachytherapy group. Patients were selected using a prospective registration study aiming at determination of our treatment results. 89 Patients (mean age 68.4 years) underwent TURT followed by a course of external beam irradiation and interstitial brachytherapy from 1983 till 2005 in the Arnhem Radiotherapy Institute. RESULTS: The median follow-up for the brachytherapy group was 5.7 years (range 0.2-21.4 years), for the cystectomy group was 5.05 years (range: 0.04-16.8 years). No difference in disease-specific survival (DSS) could be detected with a 5- and 10-year DSS of 71% and 66% in the brachytherapy group and 60% and 57% in the cystectomy group, respectively. Five-year overall survival (OS) was 57% in the brachytherapy group and 52% in the cystectomy group, however, the 10-year OS was better in the cystectomy than in the brachytherapy group (42% and 33%, respectively). This is caused by the significant age difference in favour of the cystectomy group. Cystectomy-free survival in the brachytherapy group was 70%. CONCLUSION: Radical cystectomy is the treatment of choice for patients with muscle-invasive bladder carcinoma. However, in a selected patient population a bladder sparing treatment, i.e. a combination of transurethral tumour resection (TURT), external beam irradiation and interstitial brachytherapy, can be applied successfully. This concerns a solitary, T1G3 or T2 bladder tumour, with a diameter<5 cm.

The present and future burden of urinary bladder cancer in the world.

Urinary bladder cancer (UBC) is a common disease worldwide. At any point in time 2.7 million people have a history of UBC. The incidence of UBC varies over the world with highest rates in developed communities. But the burden of UBC will increase in less developed areas of the world. These changes can be attributed to global changes in exposure to risk factors for UBC and growth and aging of the world population.

Allelic imbalance analysis using a single-nucleotide polymorphism microarray for the detection of bladder cancer recurrence.

PURPOSE: Non-muscle-invasive bladder cancer is a frequently occurring cancer, with an extremely high recurrence risk. Recurrence detection is based on cytology and urethrocystoscopy. A previous study suggested that a single-nucleotide polymorphism (SNP) array may be effective for noninvasive detection of allelic imbalances in urine. We investigated whether this method is suitable to detect allelic imbalance as an indicator of recurrences in non-muscle-invasive bladder cancer follow-up. EXPERIMENTAL DESIGN: DNA from blood and urine from 158 patients (113 with and 45 without recurrence) was hybridized to the Affymetrix GeneChip Mapping 10K 2.0. Allelic imbalance detection was based on SNPs showing changes from heterozygosity in blood to homozygosity in urine and on automatic analysis of copy number changes using Copy Number Analyser for GeneChip. RESULTS: Urine samples with tumor showed allelic imbalance at 0.4% of all informative SNPs. In samples without tumors, 0.04% of these SNPs were affected (P = 0.07). In addition, Copy Number Analyser for GeneChip analysis showed more copy number changes in samples with a tumor (P = 0.001). Losses and gains of chromosomal regions showed clustering, overlapping with known bladder cancer loci. However, 25 (22%) patients with a tumor recurrence did not display any regions with copy number changes, whereas 24 (53%) individuals without a recurrence did. Receiver operating characteristic curve analysis using the number of SNPs displaying copy number changes from the Copy Number Analyser for GeneChip analysis resulted in an area under the curve of only 0.67 (95% confidence interval, 0.58-0.76). CONCLUSION: Single-nucleotide polymorphism microarray analysis of allelic imbalance in urine cannot replace urethrocystoscopy and cytology for the detection of recurrences in non-muscle-invasive bladder cancer follow-up.

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).